↓ Figure 1. PRISMA 2020 flow diagram of the study-selection process. PICO: population, intervention, comparator, and outcomes; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
| Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access |
| Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc |
| Journal website https://jocmr.elmerjournals.com |
Original Article
Volume 18, Number 10, October 2026, pages 770-783
Balanced Crystalloids Versus Normal Saline for Fluid Resuscitation in Pediatric Septic Shock: An Updated Systematic Review and Meta-Analysis
Figures
Tables
| Study | Study design | Country | Time frame | Follow-up (days) | Sample size | Type of intervention | Inclusion criteria | Primary outcomes |
|---|---|---|---|---|---|---|---|---|
| BS: balanced salt solution; EFIC: exception from informed consent; LR: lactated Ringer; MAKE30: major adverse kidney event within 30 days; MES: multiple electrolyte solution; NZ: New Zealand; NS: normal saline; NSS: normal saline solution; NA: not available; PICU: pediatric intensive care unit; PL: Plasma-Lyte; RCT: randomized controlled trial; RLS: Ringer lactate solution. | ||||||||
| Samransamruajkit et al, 2017 [27] | Prospective observational study | Thailand | June 2013 to March 2014 | NA | 35 (20 NSS, 15 RLS) | LR | Children 1 month to 15 years with severe sepsis or septic shock | Effectiveness of balanced salt vs. 0.9% NSS on morbidity and mortality |
| Anantasit et al, 2020 [28] | Double-blind RCT | Thailand | January 2015 to December 2017 | NA | 61 (31 NS, 30 BS) | Ringer’s acetate | Children 1 month to 18 years with septic shock needing fluid resuscitation | Incidence of hyperchloremic metabolic acidosis within 48 h |
| Balamuth et al, 2019 [24] | Open-label pragmatic RCT | USA | January to August 2018 | 90 | 50 (26 NS, 24 LR) | LR | Children > 6 months to < 18 years with suspected septic shock | Feasibility (enrollment proportion, EFIC acceptability, and adherence) |
| Balamuth et al, 2026 [15] | Pragmatic multicenter clinical trial (RCT) | USA, Canada, Australia, NZ, Costa Rica | August 25, 2020 to October 31, 2025 | 90 | 8,482 analyzed (4,247 NS, 4,235 balanced) | LR, PL, or Hartmann’s solution | Children 2 months to < 18 years with suspected septic shock and abnormal perfusion | Major adverse kidney event (MAKE30) at 30 days or hospital discharge |
| Emrath et al, 2017 [9] | Observational matched cohort review | USA | January 2004 to December 2012 | 3 | 36,908 (PICU admissions) | Balanced fluids | Children 0–18 years with pediatric severe sepsis or septic shock in a PICU | In-hospital mortality |
| Sankar et al, 2023 [11] | Parallel-group, blinded multicenter trial (RCT) | India | April 10, 2017 to Jan 31, 2020 | 28 | 708 (357 saline, 351 MES) | PL A | Children up to 15 years of age with septic shock | New and/or progressive acute kidney injury within first 7 days |
| Fernández-Sarmiento 2021 [25] | Observational analytical cohort (propensity matched) | Colombia | April 1, 2018 to April 30, 2019 | NA | 99 (35 unbalanced, 64 balanced) | LR; PL | Children 1 month to 17 years with sepsis-associated organ dysfunction or shock | Presence of acute kidney injury |
| Trepatchayakorn et al, 2021 [26] | RCT | Thailand | November 2016 to November 2019 | NA | 42 | Ringer lactate; Sterofundin | Pediatric sepsis patients requiring fluid bolus | Comparison of acid–base status after fluid bolus therapy |
| Weiss et al, 2017 [10] | Matched retrospective cohort study | USA | 2000 to 2013 | 30 | 12,529 total (4,234 matched) | LR | Children < 18 years with severe sepsis/septic shock receiving fluid boluses | All-cause 30-day hospital mortality |
| Study ID | Groups | Patient demographics | Hemodynamic parameters, mean ± SD | Focus of infection, n (%) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Age (years) | Weight (kg) | Male, n (%) | SOFA score | PRISM III score | Lactate (mmol/L) | Pulmonary | Urinary | Skin/soft tissue | ||
| aFor this study (Fernandez-Sarmiento 2021 [25]), the published overall-cohort age was median 9.9 months (IQR 4.9–22.2); arm-specific age and PRISM III summary values could not be independently verified and are shown as NA. Other mean ± SD entries are reproduced as shown in the source table. BS: balanced salt solution; NS: normal saline; NA: not available; SOFA: sequential organ failure assessment; SD: standard deviation. | ||||||||||
| Samransamruajkit et al, 2017 [27] | BS | 6.4 ± 4.8 | 24.28 ± 17.7 | 9 (60) | 6.67 ± 2.02 | 5.40 ± 4.64 | NA | 18 (51.4) | 4 (11.4) | 5 (14.3) |
| NS | 4.2 ± 4.9 | 17.27 ± 14.89 | 12 (60) | 8.30 ± 2.64 | 8.75 ± 4.64 | NA | ||||
| Anantasit et al, 2020 [28] | BS | 6.03 ± 8.33 | NA | 14 (46.7) | NA | 7.83 ± 7.79 | 1.83 ± 1.09 | 8 (26.7) | NA | NA |
| NS | 6.25 ± 7.31 | NA | 22 (70.9) | NA | 9.67 ± 10.89 | 2.4 ± 1.4 | 5 (16.1) | NA | NA | |
| Balamuth et al, 2019 [24] | BS | 5.4 ± 6.62 | NA | 13 (54) | NA | NA | NA | 5 (21) | 4 (17) | 2 (8) |
| NS | 9.53 ± 10.8 | NA | 14 (54) | NA | NA | NA | 5 (19) | 3 (12) | 3 (12) | |
| Balamuth et al, 2026 [15] | BS | 7.47 ± 7.42 | NA | 2166 (51.2) | NA | NA | 2.07 ± 1.26 | 46.6% | NA | NA |
| NS | 7.47 ± 7.42 | NA | 2136 (50.4) | NA | NA | 2.07 ± 1.26 | NA | NA | ||
| Emrath et al, 2017 [9] | BS | 6.0 ± 6.1 | NA | 1308 (54.5) | NA | NA | NA | NA | NA | NA |
| NS | 7.4 ± 6.3 | NA | 15891 (52.7) | NA | NA | NA | NA | NA | NA | |
| Sankar et al, 2023 [11] | BS | 4.67 ± 5.96 | NA | 201 (57) | 7 ± 4.47 | NA | NA | 149 (42) | 7 (2) | 5 (1) |
| NS | 5.17 ± 5.59 | NA | 205 (58) | 7 ± 4.47 | NA | NA | 129 (36) | 10 (3) | 6 (2) | |
| Fernandez-Sarmiento 2021 [25] | BS | NAa | NA | 35 (55.5) | NA | NAa | NA | 37 (58.73) | 3 (4.76) | 3 (4.76) |
| NS | NA | 19 (55.5) | NA | NA | 19 (52.78) | 4 (11.11) | 4 (11.11) | |||
| Trepatchayakorn et al, 2021 [26] | BS | NA | NA | 24 (57.1) | NA | 4 | 4.1 ± 5.57 | NA | NA | NA |
| NS | NA | NA | NA | 2.07 ± 1.43 | NA | NA | NA | |||
| Weiss et al, 2017 [10] | BS | 8 ± 10.39 | NA | 1,119 (53) | NA | NA | NA | NA | NA | NA |
| NS | 7.33 ± 9.65 | NA | 1,149 (54) | NA | NA | NA | NA | NA | NA | |